422 results
Search Results
2. Gut microbiota and intestinal immunity—A crosstalk in irritable bowel syndrome.
- Author
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Chen, Yuxuan, Feng, Shuyan, Li, Ying, Zhang, Chi, Chao, Guanqun, and Zhang, Shuo
- Subjects
- *
IRRITABLE colon , *GUT microbiome , *VISCERAL pain , *IMMUNITY , *ABDOMINAL pain - Abstract
Irritable bowel syndrome (IBS), one of the most prevalent functional gastrointestinal disorders, is characterized by recurrent abdominal pain and abnormal defecation habits, resulting in a severe healthcare burden worldwide. The pathophysiological mechanisms of IBS are multi‐factorially involved, including food antigens, visceral hypersensitivity reactions, and the brain–gut axis. Numerous studies have found that gut microbiota and intestinal mucosal immunity play an important role in the development of IBS in crosstalk with multiple mechanisms. Therefore, based on existing evidence, this paper elaborates that the damage and activation of intestinal mucosal immunity and the disturbance of gut microbiota are closely related to the progression of IBS. Combined with the application prospect, it also provides references for further in‐depth exploration and clinical practice. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
3. Recovery training or over‐training? The contribution of TLR10 to monocyte fitness.
- Author
-
Rodgers, Lewis and Milling, Simon
- Subjects
ACTIVE recovery ,NATURAL immunity ,IMMUNITY - Abstract
Summary: The concept of trained immunity refers to remodelling of the monocyte and macrophage metabolic and epigenetic landscape, conferring an amplified inflammatory response upon secondary stimulation. This effect is typically modelled in vitro by stimulating monocytes with either Bacillus Calmette Guerin (BCG) or β‐Glucan for 24 hr, before subsequent stimulation with LPS or Pam‐3‐Cys (P3C) as a secondary stimulus 6 days later. Here, we focus on a recent paper which interrogated the role of the anti‐inflammatory TLR, TLR10, on trained immunity. Using both an in vitro model of trained immunity, and analysis of BCG vaccinated individuals, the authors interestingly demonstrate that, despite its ability to regulate aspects of innate immunity, TLR10 does not have a significant role in this process. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
4. Immunochemical properties of some monoclonal IgE antibodies to 4-hydroxy-3-nitrophenylacetyl (NP).
- Author
-
Bose, R., Bundesen, P. G., Holford-Stevens, V., Stefura, W. P., Kelly, K. A., Jeffrey, J. C., Rector, E. S., Fischer, J., Sehon, A. H., and Schwenk, R. J.
- Subjects
IMMUNOGLOBULIN E ,IMMUNOGLOBULINS ,MONOCLONAL antibodies ,IMMUNOCHEMISTRY ,IMMUNITY ,CELL lines ,CELL culture - Abstract
Several hybridoma cell lines secreting NP-specific, murine IgE antibodies were generated by fusion of P3-X20 (γ,κ) tumour cells with spleen cells from (BALB/c x C57Bl/6)F
1 (CB6F1 ) mice previously immunized with NP-ovalbumin. Four subclones (designated NP-ε-3.57, NP-ε-15,88, NP-ε-91,58 and NP-ε-95,31) were propagated in vivo and milligram quantities of the corresponding IgE antibodies were purified from ascitic fluid by gel filtration, ion exchange chromatography and affinity chromatography. Immunological analyses and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDSPAGE) indicated that NP-ε-15,88, NP-ε-91,58 and NP-ε-95.31 all possessed λ1 (or possibly λ3 ) light chains; and that NP-ε-3,57 possessed λ2 light chains; NP-&elipson;-95,31 also expressed the P3-X20 derived, MOPC-21 κ light chain. Radioallergosorbent test (RAST) titration curves, generated from the interaction of the four monoclonal IgE antibodies with NP-BSA attached to paper discs (NP-BSA-P) were found to be non-overlapping. Measurements of the relative amounts of NP-ε-aminocaproic acid (NP-CAP) and 4-hydro-3-iodo-5-nitrophenylacetyl-ε- aminocaproic acid (NIP-CAP) that were required to inhibit by 50% the binding of the 4 IgE antibodies to NP-BSA-P indicated that these antibodies were all heteroclitic, since their affinity for NIP appeared to be higher than their affinity for NP. These results, in conjunction with other findings reported in the literature, suggested that the V regions of NP-specific IgE antibodies are similar to the V regions of NP-specific IgM and IgG antibodies, produced by the same mouse strains. Finally, in vitro histamine release measurements demonstrated that two of these monoclonal IgE antibodies could mediate antigen induced histamine release from passively sensitized rat peritoneal mast cells. [ABSTRACT FROM AUTHOR]- Published
- 1984
5. Grass Pollen Allergens III.--THEIR DIFFERENTIATION FROM THE OTHER POLLEN ANTIGENS BY IMMUNO-ELECTROPHORETIC STUDIES IN RELATION TO SKIN REACTIVITY, ENZYMIC DIGESTIONS, HEAT AND <em>p</em>H STABILITIES.
- Author
-
Augustin, Rosa
- Subjects
ORCHARD grass ,POLLEN ,ALLERGENS ,ANTIGEN-antibody reactions ,ANTIGENS ,IMMUNOGLOBULINS ,IMMUNITY - Abstract
Heat and pH stability studies and experiments with organic solvents show that the A-antigens discussed in the preceding paper (Augustin, 1959c) are much more labile than the I-(‘inner ring’) antigens. Breakdown products and/or aggregates are produced which no longer precipitate with antisera to the original extracts, but act as inhibitors. Solutions of pollen allergens, on the other hand, are found to withstand even autoclaving for 15 min. at 20 atm. and vigorous boiling over the naked flame of a bunsen burner. None of the carbohydrates tested has a demonstrable effect on skin reactivity which is, however, destroyed by crystalline pepsin, crystalline trypsin, a crystalline mould protease and a tissue protease (a partially purified extract from rabbit spleen). It follows that the bulk of the allergens—if not all—are proteins. The relation of skin reactivity, immuno-electrophoretic patterns, carbohydrate and protein reactions to the selective destruction of the pollen antigens is investigated. Pollen components prove to have a somewhat wider range of electrophoretic mobilities than serum proteins and are probably as complicated a mixture. The most and least highly negatively charged components are without skin reactivity in allergic subjects. The skin reactive allergens appear to have the mobilities of α- and β-globulins. Not all the hay fever subjects react equally to all the components, and Cocksfoot and Timothy activity patterns vary in different subjects. [ABSTRACT FROM AUTHOR]
- Published
- 1959
6. The sensitivity of rat CD8+ and CD4+ T cells to ricin <em>in vivo</em> and <em>in vitro</em> and their relationship to IgE regulation.
- Author
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Diaz-Sanchez, D. and Kemeny, D. M.
- Subjects
LYMPHOID tissue ,TOXINS ,MURIDAE ,IMMUNITY ,T cells ,LACTOSE - Abstract
In a previous paper we described how the toxin ricin stimulates IgE but not IgG antibody responses in rats. In this study we have examined the cellular basis for this observation. The proportion of CD4
- and CD8- positive cells present in the spleen at the peak of the IgE response was determined. Those animals injected with both ricin and antigen produced a substantial IgE response (50-fold increase). Their CD4+ /CD8+ ratio was also markedly increased (P> 0.001l)compared with animals given toxin or antigen alone. In addition, mitogen-stimulated proliferation of mononuclear cells from spleens of the IgE-producing rats was enhanced nearly five-fold compared with cells from animals given toxin or allergen alone. The sensitivity of CD4- and CD8- positive rat spleen cells from unexposed animals to ricin in vitro was also studied. Spleen cells from untreated rats were co-cultured with optimal doses of mitogen and varying amounts of ricin. Mitogen-driven proliferation was inhibited at l0-3 -10-6 mg/ml ricin. This effect was abrogated by the addition of as little as 0.01 m lactose but not by as much as 10 mg/mI mannan to the culture. Cultures depleted of CD4+ cells by rosetting were approximately 100 times more sensitive to ricin (P>0.01). Furthermore, the proportion of CD8+ to CD4+ cells present after culture of untreated cells with mitogen and ricin was significantly reduced. These results show (i) that the ability of ricin to increase the IgE response depends on the administration of antigen together with the toxin; (ii) that CD8+ spleen cells are more sensitive to ricin than CD4+ cells; (iii) that increased IgE responsiveness is associated with a reduction in the proportion of CD8- relative to CD4- positive cells in the spleen and increased responsiveness to mitogen. We believe that enhancement of the IgE responses by ricin may be due to inactivation of IgE-specific T-suppressor cells generated by immunization with antigen and speculate that these may be some or all of those bearing the CD8 marker. [ABSTRACT FROM AUTHOR]- Published
- 1990
7. T-cell activation: I. EVIDENCE FOR A FUNCTIONAL LINKAGE BETWEEN CLASS I MHC ANTIGENS AND THE TC--TI COMPLEX.
- Author
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Brams, P. and Claesson, M. H.
- Subjects
MHC antibodies ,IMMUNOGLOBULINS ,T-cell receptor genes ,ANTIGENS ,IMMUNITY ,AMINO acids - Abstract
This paper examines the possibility of a functional linkage between class I MHC molecules and the T-cell receptor complex for antigen (T3-Ti). A newly developed anti-CD3 antibody (500A2) was used as an activation signal for EL4 lymphoma cells and allospecific cytotoxic T-cell clones (CTL), and the production of IL-2/IL-2 receptor in EL4 cells and serine esterase in CTL was determined. Anti-CD3 antibody-induced activation of both EL4
+ and CTL cells was enhanced in the presence of immunologically cross-linked and immobilized anti-H-2 (class I) antibody reactive against the H-2 haplotype of the responding T cells. A number of H-2-negative and H-2-positive EL4 subclones were generated and tested for anti-CD3 antibody-induced IL-2/IL-2 receptor production. Although both H-2-positive and -negative subclones expressed CD3 antigen and produced IL-2 after activation with the phorbol ester TPA, only the H-2-positive cell clones produced IL-2 and expressed IL-2 receptor after anti-CD3 antibody induction. Our results are compatible with the existence of a functional linkage between the class I and the CD3 molecules on the surface of T cells. [ABSTRACT FROM AUTHOR]- Published
- 1989
8. Enhancement of immunity against RSV-induced sarcomas by generation of hapten-reactive helper T lymphocytes.
- Author
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Comoglio, P. M., Prat, Maria, and Bretti, S.
- Subjects
ROUS sarcoma ,IMMUNITY ,LYMPHOCYTES ,T cells ,TUMORS ,LABORATORY mice - Abstract
Previous work from this laboratory has shown that preimmunization of syngeneic hosts with Rous sarcoma virus (RSV)-transformed cells elicits a strong immune response against the growth of transplantable RSV sarcomas, mediated by T lymphocytes expressing the surface phenotype of helper cell precursors (Prat, Di Renzo & Comoglio, 1983). This paper shows that anti-tumour immunity may be elicited in tumour-bearing animals by triggering an experimentally pre-amplified T-helper cell population at the site of tumour growth. Mice were treated with cyclophosphamide (which inactivates suppressor T cells) followed by skin sensitization to trinitrochlorobenzene (TNCB) according to a protocol that has been shown to induce an appreciably amplified generation of trinitrophenyl (TNP)-reactive helper T cells (Fujiwara et al., 1984). Five weeks after TNCB painting, mice were transplanted s.c. with a lethal dose of RSV-induced syngeneic sarcoma cells; the injection at the tumour site of TNCB induced the regression of the tumour in mice in which the TNP-helper cell population has been amplified, but not in controls, including those injected with a non-related hapten or sensitized to TNCB without inactivation of suppressors. [ABSTRACT FROM AUTHOR]
- Published
- 1985
9. Desensitization <em>in vitro</em>: the role of T-suppressor cells, T-suppressor factor and T-acceptor cells in the inhibition of the passive transfer of contact sensitivity to picryl chloride by exposure to antigen <em>in vitro</em>.
- Author
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M. Zembala, Asherson, G.L., Colizzi, V., and Watkins, Madeleine C.
- Subjects
T cells ,LYMPHOCYTES ,IMMUNITY ,IMMUNOLOGY ,ANTIGENS ,LYMPH nodes ,SPLEEN - Abstract
This paper investigates desensitization in vitro, e.g. the inhibition of the transfer of contact sensitivity to picryl chloride by incubation of the passive transfer population with picrylated spleen cells. It asks whether desensitization is based on the same T-suppressor circuit which is responsible for the inhibition of passive transfer by antigen-specific T-suppressor factor (TsF). In this circuit, the T-suppressor cell which acts at the efferent stage (Ts-eff) makes TsF. This TsF depresses contact sensitivity indirectly by arming a T-acceptor cell (Tacc). The armed Tacc, when exposed to antigen (picrylated spleen cells), liberates a non-specific inhibitor which blocks the transfer of contact sensitivity. The three elements of this T-suppressor circuit occur in nylon wool-purified T cells prepared from the lymph nodes and spleens of mice four days after immunization with picryl chloride. This population transfers contact sensitivity and can be desensitized in vitro. It contains Ts-eff which can be isolated by panning (adherence) on picrylated albumin and detected by their ability to inhibit passive transfer. The 24 hr supernatant of cultures of these cells contains TsF. Finally the population contains Tacc which appear in the spleen 2 days after immunization and virtually disappear by 10 days. Further experiments demonstrated that the Ts-eff and the Tacc were not merely present but actually required for desensitization in vitro. Immune cells depleted of both Ts-eff (by panning on picrylated albumin) and Tacc (by arming with anti-oxazolone TsF and panning on oxazolonated albumin) cannot be desensitized. To restore desensitization both Ts-eff and Tacc must be added back. The Ts-eff were characterized as cyclophosphamide resistant, adult thymectomy sensitive cells (Cy
r , ATx5 ), which adhered to antigen and were produced only by specific immunization. The Tacc were characterized as CF5 , ATx5 cells which adhered to antigen only after arming with antigen-specific T-suppressor factor and were produced after immunization with an unrelated contact sensitizer, 'oxazolone'. It was concluded that desensitization in vitro was due to the interaction of two distinct T cells: the T-suppressor cell which acts at the efferent stage of the contact sensitivity reaction and the T-acceptor cell which becomes armed with the specific T-suppressor factor produced by the Ts-eff. [ABSTRACT FROM AUTHOR]- Published
- 1982
10. Migration inhibition of lymph node lymphocytes as an <em>in vitro</em> assay for cell-mediated immunity in the draining lymph nodes of parenterally immunized mice.
- Author
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Mowat, A. Mcl. and Ferguson, Anne
- Subjects
LYMPHOCYTES ,LEUCOCYTES ,LYMPH nodes ,IMMUNITY ,IMMUNOLOGY - Abstract
This paper describes a method for in vitro measurement of specific cell-mediated immunity in the mouse. Animals were immunized parenterally with ovalbumin in Freund's incomplete or complete adjuvant, and a direct migration inhibition assay was performed, using lymphoid cells from the draining lymph nodes. Migration inhibition was found to be antigen specific, correlated with systemic delayed-type hypersensitivity measured in vivo by skin testing, and had a high degree of sensitivity for ovalbumin. The migrating cells were identified as lymphocytes. Lymph node lymphocyte migration inhibition provides a reliable in vitro assay for regional CMl in the mouse. [ABSTRACT FROM AUTHOR]
- Published
- 1982
11. Reversible binding of a guinea-pig lymphokine to gelatin and fibrinogen: possible relationship of macrophage agglutination factor and fibronectin.
- Author
-
Godfrey, H. P. and Purohit, A.
- Subjects
LYMPHOKINES ,GUINEA pigs ,GELATIN ,FIBRINOGEN ,AGGLUTINATION ,FIBRONECTINS ,IMMUNITY - Abstract
Macrophage agglutination factor (MAggF) is a T-cell-dependent guinea-pig lymphokine with pH stability, heat stability and isoelectric point similar to fibronectin (see preceeding paper for details). Further observations confirm the similarity between MAggF and fibronectin. MAggF in unconcentrated lymph node cell culture supernatants bound reversibly to gelatin and fibrinogen. On gel filtration chromatography, most MAggF activity in a pooled concentrated lymphokine preparation was associated with molecules of 370,000 Daltons; lesser amounts of activity were found at 240,000 and 50,000 Daltons. All molecular weight forms of MAggF bound reversibly to gelatin. Guinea-pig plasma fibronectin prepared by affinity chromatography over gelatin had a molecular weight of about 450,000, a sub-unit on reduction of about 240,000 Daltons, and showed partial antigenic identity with human plasma fibronectin. Human and guinea-pig plasma fibronectin preparations showed MAggF activity when tested using guinea-pig peritoneal macrophages, but their potencies relative to a culture supernatant standard did not correlate with the content of immunoprecipitable fibronectin measured by anti-human fibronectin antiserum. However, anti-human fibronectin immunoadsorbents specifically and reversibly bound MAggF activity in culture supernatants. On the basis of our observations, we suggest MAggF is a guinea-pig tissue fibronectin. [ABSTRACT FROM AUTHOR]
- Published
- 1982
12. Characterization of immunogenic properties of haptenated liposomal model membranes in mice: IV. INDUCTION OF IgM MEMORY.
- Author
-
Van Houte, A. J., Snippe, H., and Willers, J. M. N.
- Subjects
IMMUNOGENETICS ,LIPOSOMES ,IMMUNITY ,IMMUNOGLOBULINS ,MEMORY ,MICE - Abstract
This paper describes the induction of IgM immune memory to haptenated liposomes in mice. The tripeptide-enlarged haptens 3-(p-azo-benzene-arsonate)-N-acetyi-L-tyrosylglycyiglycine (A) and N-(2,4-dinitrophenyl)-β-alanylglycylglycine (J) were coupled to phosphatidylethanola mine (PE) and the conjugates A-PE and J-PE were incorporated into separate liposomal membranes (monofunctional A-PE-liposomes or J-PE-Liposomes) or into the same liposomal membranes [bifunctional (A,J)PE-liposomes]. The magnitude of the humoral response was measured by the appearance of direct and indirect plaque-forming cells in the spleens of immunized mice. Intracutaneous priming of mice with A-PE-liposomes mixed with the adjuvant dimethyl dioctadecyl ammonium bromide (DDA) and secondary immunization with bifunctional (A.J)-PE-liposomes resulted in enhanced hapten A- and J-specific IgM responses. However, no switch from IgM to IgG antibodies was observed in these mice. The J-specific IgM response was enhanced only when hapten I was incorporated into a bifunctional liposome which also contained A-epitopes. in mice primed with A-PE-liposomes in the absence of DDA, a greatly diminished memory to both hapten A and J was observed. This finding indicates a crucial role for the adjuvant in the induction of memory. J-PE-liposomes and DDA were not able to induce memory to monofunctional J-PE-liposomes or bifunctional (A,J)-PE-liposomes. The possibility that hapten A-specific B lymphocytes were responsible for the induction of memory was excluded by hapten-specific blockade of these cells with a B-cell tolerogen. These data, in addition to the observation that no IgM memory could be induced in congenitally athymic nude mice, suggest that the observed memory can be ascribed to priming of hapten A-specific T lymphocytes. [ABSTRACT FROM AUTHOR]
- Published
- 1981
13. Numerical immunotaxonomy of <em>Leishmania</em> I. DIFFERENTIATION OF FOUR STRAINS OF <em>LEISHMANIA</em> BY SEROLOGICAL TESTS.
- Author
-
Matossian-Rogers, A., Lumsden, W. H. R., and Dumonde, D. C.
- Subjects
LEISHMANIA ,IMMUNOCYTOCHEMISTRY ,PARASITES ,IMMUNITY ,BLOOD plasma ,IMMUNE serums - Abstract
This paper describes the application of numerical methods to the arrangement of four leishmanial strains according to their reactivity and cross-reactivity in tests of parasite agglutination, indirect immunofluorescence and passive cutaneous anaphylaxis with antisera prepared by immunization or infection of rabbits, guinea-pigs and mice. Using corresponding pools of animal sera as test 'reagents' the antigenic reactivity of the four leishmanial strains (L. enriettii, L. tropica major, L. aethiopica and L. mexicana amazonensis) was scaled by reference to end point serum titres; and antigenic relationships between individual strain pairs were expressed as mean similarity coefficients, giving equal weight to the results of the different serological tests. Overall analysis of the results revealed that L. mexicana amazonensis and L. tropica major were the two most closely related strains, clustering with an overall similarity coefficient of 89 per cent, whereas coefficients of similarity between other strain combinations fell between 75 and 80 per cent. Although different sera had different discriminatory capacity for the leishmanial strains, two combinations of serum reagent and test system yielded relationships between the four strains that most closely approximated to the overall values. These were: (a) immunofluorescence tests with mouse antisera; and (b) agglutination tests with selected rabbit antisera. The results illustrate the use of a number of immunological parameters in relatingmicro organisms of a given genus, and reveal a serological classification of the four leishmanial strains at variance with their geographical origin. [ABSTRACT FROM AUTHOR]
- Published
- 1976
14. Brown Adipose Tissue and Immunity: EFFECT OF NEONATAL ADIPECTOMY ON HUMORAL AND CELLULAR IMMUNE REACTIONS IN THE RAT.
- Author
-
Janković, B.D., Janežić, Alenka, and Popesković, Ljiljana
- Subjects
ADIPOSE tissues ,IMMUNITY ,LIPECTOMY ,IMMUNE system ,LABORATORY rats ,ERYTHROCYTES - Abstract
This work concerns the involvement of brown adipose tissue in the immune system of the rat. Wistar rats were thymectomized, adipectomized (surgical extirpation of the interscapular brown adipose tissue), thymectornited and adipectomized, and. sham,operated at birth, only 8-week-old females being employed in the experiment The production of antibody to bovine serum albumin (BSA). and sheep red blood cells (SRBC), delayed skin reactions to BSA, rejection of thyroid allograft implanted under the kidney capsule, and development of experimental allergic encephalomyelitis were investigated. Neonatal adipectomy did not affect the production of anti-BSA and anti-SRBC antibodies. On the other hand, delayed skin reactions to BSA, rejection of thyroid allograft, and incidence and severity of allergic encephalomyelitis were much more pronounced In adipectomized animals. It has been postulated that the immune function of brown adipose tissue is an expression of the secretory activity of the tissue. Since the immunosuppressive effect of neonatal thymectomy on demyelinating disease was neutralized by neonatal adipectomy, and vice versa, and since thymectomy rendered ineffective the immunopotentiating influence of adipectomy on this disease, as demonstrated in thymo-adipectomized rats, it was concluded that the brown adipose tissue is a natural antagonist of the thymus in cell-mediated immunity. This paper also describes the extra thymuses which were situated in the vicinity of the thyroid and parathyroid lobes of 23.2 per cent of rats. [ABSTRACT FROM AUTHOR]
- Published
- 1975
15. Antigen-binding Small Lymphocytes in the Guinea-pig II. THE IMMUNOLOGICAL RESPONSE TO PURIFIED PROTEIN DERIVATIVE OF MAMMALIAN TUBERCULIN.
- Author
-
Donald, D., King, D. J., and Beck, J. Swanson
- Subjects
ANTIGENS ,IMMUNITY ,IMMUNOGLOBULINS ,LYMPHOCYTES ,IMMUNE system ,GUINEA pigs - Abstract
A mean of 6.9 per cent of small lymphocytes in peripheral blood preparations and between 1.8 and 2.4 per cent of small lymphocytes in lymph node, spleen, bone marrow and thymus preparations from unimmunized guinea-pigs bound
125 I-labelled purified protein derivative of mammalian tuberculin (mammalian PPD). The percentage of these cells fluctuated but did not alter substantially after immunization with BCG or with BCG emulsified with human thyroglobulin (HTg) in Freund's incomplete adjuvant (FIA). Blocking experiments indicated that the binding of125 I-labelled mammalian PPD was specific and there was tentative evidence that the lymphocyte receptors may be IgG. A comparison is drawn between the observed time course of125 I-labelled mammalian PPD- binding small lymphocytes and the response of lymphocytes sensitive to strong histocompatibility antigens, and it is proposed that the propensity of certain anti- gens to induce a delayed hypersensitivity-type response is related to the presence of substantial numbers of antigen-binding cells in unimmunized animals. A noteworthy incidental finding was an unexplained depression in the cellular and humoral responses to mammalian PPD in guinea-pigs that had been immunized with HTg-BCG-FIA emulsion. [ABSTRACT FROM AUTHOR]- Published
- 1974
16. <em>In vitro</em> Stuides of 'Antigenic Competition' II. RECONSTITUTION OF THE IMMUNE DEFECT AND THE RELATIONSHIP BETWEEN ANTIGEN-INDUCED SUPPRESSION AND NON-SPECIFIC ENHANCEMENT.
- Author
-
Pross, H. and Eidinger, D.
- Subjects
IMMUNITY ,IMMUNOLOGY ,ANTIGENS ,CELLULAR immunity ,IMMUNE response ,IMMUNE recognition - Abstract
The experiments described in this paper extend the observations of previous work in vitro demonstrating a decrease in the frequency of antigenreactive units specific for horse RBC in spleen cells from mice primed with KLH. It was observed that the addition of lymphoid cells having T-cell function reconstituted the anti-HRBC response to normal values. Significant enhancement of the response beyond the normal values could be evoked using two dissimilar methods, (i) addition of allogeneic thymus cells, and (ii) restimulation in vitro with the priming antigen. The latter type enhancement was elicited by the addition of small doses of KLH to cultures of spleen cells from mice recently primed with KLH, including cultures otherwise demonstrating antigen-induced suppression. The stimulus required to enhance the response to HRBC in these cultures was specific for the priming antigen, KLH. These results are discussed in the light of current theories of 'antigenic competition' and specific heterologous enhancement. [ABSTRACT FROM AUTHOR]
- Published
- 1973
17. Thymocyte emigration in the chicken: an over-representation of CD4+ cells over CD8+ in the periphery.
- Author
-
Katevuo, K.
- Subjects
CD antigens ,GLYCOPROTEINS ,FC receptors ,CELL surface antigens ,IMMUNOGLOBULINS ,IMMUNITY - Abstract
We have examined the emigration of chicken thymocytes after intrathymic fluorescein isothiocyanate (FITC) labelling in situ. In this paper we show that in young birds about 0.7% and 0.4% of thymocytes emigrate from the thymus to the blood and the spleen, respectively, per day. This suggests that, as in mammals, most thymocytes die within the thymus. At 3 weeks of age γδ and αβ T cells leave the thymus in comparable levels to their appearance in the blood. The phenotype of recent emigrants in peripheral tissues is similar to that of mature T cells. Interestingly, recent emigrants contain relatively much higher numbers of CD4
+ and fewer CD8+ cells than is observed in peripheral tissues in a steady-state situation. [ABSTRACT FROM AUTHOR]- Published
- 1996
- Full Text
- View/download PDF
18. Regulation of T-cell activation in the lung: isolated lung T cells exhibit surface phenotypic characteristics of recent activation including down-modulated T-cell receptors, but are locked into the G0/G1 phase of the cell cycle.
- Author
-
Strickland, D., Kees, U. R., and Holt, P. G.
- Subjects
T cells ,LUNGS ,IMMUNITY ,RESPIRATORY organs ,LYMPHOCYTES ,ANTIGENS ,MACROPHAGES - Abstract
Peripheral lung tissue contains large numbers of T cells, strategically located for immune surveillance at the blood-air interface. Given the intensity of antigenic exposure at this site, it is clear that local T-cell activation events require strict control, in order to maintain tissue homeostasis. How this control is achieved in this unique tissue microenvironment is unknown, and the present study sought to elucidate the process via detailed analysis of the surface phenotypic characteristics of freshly isolated lung T cells. We report below that these cells display typical characteristic of ‘postactivation’, notably elevated basal Ca
2+ concentrations, down-modulated T-cell receptors, expression of Ia and ‘late’ activation antigens and concomitant CD4/CD8. However, levels of interleukin-2 receptor and CD2 expression were below those expected of ‘activated’ T-cell populations, and virtually all of the cells were found to be in the G0 /G1 phases of the cell cycle. These properties bear a remarkable similarity to those of T cells activated in the presence of endogenous tissue (alveolar) macrophages from the lung (see accompanying paper). We hypothesize that they reflect the in vivo operation of an endogenous macrophage-mediated T-cell anergy-induction process, the function of which is to limit the local clonal expansion of T cells in peripheral lung tissue after in situ activation. [ABSTRACT FROM AUTHOR]- Published
- 1996
- Full Text
- View/download PDF
19. Major histocompatibility complex control of the class of the immune response to the hapten trinitrophenyl.
- Author
-
Sjölander, A., Andersson, R., Hansson, M., Berzins, K., and Perlmann, P.
- Subjects
MAJOR histocompatibility complex ,IMMUNOGENETICS ,IMMUNE response ,IMMUNOLOGY ,IMMUNITY ,HAPTENS - Abstract
This paper investigates major histocompatibility complex (MHC) regulation of the class of the immune response given in vitro and in vivo following immunization of the congenic BALB/k (H-2
k ) and BALB/c (H-2d ) mice with the hapten trinitrophenyl (TNP). TNP-immune lymph node cells from BALB/k mice produced high levels of interferon-γ (IFN-γ), interleukin-5 (IL-5) and IL-2 when stimulated with TNP-antigen-presenting cells (APC) in vitro, while TNP-immune lymph node cells from BALB/c mice produced very low levels of these cytokines. No significant difference was found in antigen-specific production of IL-3, IL-4 and tumour necrosis factor-α (TNF-α). There was a strong correlation between the pattern of cytokine production in vitro and the secondary antibody production in vivo. Sera from BALB/k mice had anti-TNP IgG2a, IgG2b and IgG3 levels threefold greater, and anti-TNP IgA levels eightfold greater, than BALB/c mice. The level of specific IgG1 and IgE was only marginally raised in BALB/k mice. In contrast to these strain differences in cytokine and antibody production, there was no difference in two measures of cellular immunity: contact sensitivity in vivo and antigen-specific lymphocyte response in vitro. Our results suggest that there is a good correlation between the production of cytokines in vitro and antibody response in vivo, but not with measures of cellular immunity. Moreover, this MHC control of the class of the immune response to TNP does not fit into the T-helper type-1 (Th1)-Th2 paradigm. [ABSTRACT FROM AUTHOR]- Published
- 1995
20. Multiple Nature of the Third Component of Guinea-Pig Complement II. SEPARATION AND DESCRIPTION OF TWO ADDITIONAL FACTORS β AND <em>d</em>; PREPARATION AND CHARACTERIZATION OF FOUR INTERMEDIATE PRODUCTS.
- Author
-
Klein, P. G. and Wellensier, H. J.
- Subjects
EXPERIMENTAL immunology ,IMMUNOLOGY ,IMMUNITY ,GUINEA pigs as laboratory animals ,ANIMAL models in research - Abstract
Two factors essential for the lysis of EAC'
142 cells are described and designated as Β and d. These factors are distinct from the C'3 -subunits a, b and c described earlier; they can be separated by chemical procedures. A simple assay method for both factors is given. Four highly reactive intermediates, EAC'142 ,a; EAC'142 ,a,b; EAC'142 ,a,b,Β and EAC'142 ,a,b,Β,c can be prepared and characterized by their lytic reactivity pattern against different systems of incomplete C'3 . Evidence is presented that the subunits of the C'3 -system interact with EAC'142 in a sequential order corresponding to the formula a-b-Β-c-d. [ABSTRACT FROM AUTHOR]- Published
- 1965
21. Studies on Production of Biologically Active Substances which Inhibit Cell Migration in Supernatants and Extracts of Hypersensitive Lymphoid Cells Incubated with Specific Antigen <em>In vitro</em>.
- Author
-
Švejcar, J., Pekárek, J., and Johanovský, J.
- Subjects
LYMPHATICS ,ANTIGENS ,IMMUNITY ,IMMUNOGLOBULINS ,ALLERGENS ,ANTIGEN-antibody reactions - Abstract
When lymphoid cells from hypersensitive rabbits are incubated with antigen, biologically active substances are formed and released which are capable of inhibiting the migration of normal non-sensitized mesenchymal cells. In the present paper some basic parameters of their production were determined. These substances were regularly obtained after 6 and 18 hours incubation, but not after 2 hours. Under more favourable cultivation conditions (lower density of lymphocyte suspension) an increased activity in the cell extracts as compared with the supernatants was observed. Another critical factor in the production of these substances is the quantity of antigen added. Ten micrograms of PPD leads to the production and liberation of a highly effective substance. A lower dose of antigen results in the liberation of a substance into the supernatant which by itself is almost inactive, but becomes more active when more antigen is added. The efficiency of the released substances was determined by serial dilution. The inhibiting activity was maintained at 1:5 and 1:20 and sometimes at 1:100 dilutions. [ABSTRACT FROM AUTHOR]
- Published
- 1968
22. Reactive Haemolysis -- A Distinctive Form of Red Cell Lysis.
- Author
-
Thompson, R. A. and Rowe, D. S.
- Subjects
ANTIGEN-antibody reactions ,ERYTHROCYTES ,HEMOLYSIS & hemolysins ,SERUM ,IMMUNITY ,EXPERIMENTAL pathology - Abstract
This paper describes a form of red cell lysis differentiated from classical complement haemolysis by its occurrence in the absence of antibody on the cells and in the presence of EDTA. This type of haemolysis has been called reactive haemolysis. It is the result of the interaction, in the presence of red cells, of at least two serum factors called ‘reactor’ and ‘indicator’, respectively. Reactor only becomes active after incubation at 37° of serum with certain agents, notably antibody-coated bacteria, zymosan and agarose, in conditions similar to those required for complement activation. The potential for the formation of activated reactor could be demonstrated infrequently in healthy subjects but more frequently in sera from hospital patients. Activated reactor behaved as a protein sedimenting between 7S and 19S, and of α
2 -β1 , electrophoretic mobility in agar. Indicator factors were present in all human sera studied, as well as in the sera of a number of mammalian species. They were demonstrable at high dilutions of the serum and required no prior activation for their action. They occurred maximally in the 7S fractions of serum proteins and migrated in the β2 position on electrophoresis. Reactive haemolysis was first observed and can most conveniently lie demonstrated in a red cell-agarose gel. It can also be demonstrated in the test tube following partial purification of activated reactor and indicator factors. Studies in the test tube indicated that a .soluble labile lytic factor was responsible for this type of haemolysis, [ABSTRACT FROM AUTHOR]- Published
- 1968
23. Immunochemical Characterization of Submicrosomal Rat Liver Membranes.
- Author
-
Lundkvist, U. and Perlmann, P.
- Subjects
IMMUNOGLOBULINS ,BLOOD proteins ,ENDOPLASMIC reticulum ,IMMUNITY ,IMMUNOLOGY ,ANIMAL models in research - Abstract
Rat liver microsomes were separated into three subfractions by means of ultracentrifugation through sucrose media of different densities and in the presence of different cations. Detergent extracts of these preparations were analysed by double diffusion in agar gel and immunoelectrophoresis with rabbit antisera against each of the subfractions. One subfraction was derived from the ‘rough’ and another from the ‘smooth’ part of the endoplasmic reticulum of the liver parenchymal cells. Their extracts contained at least thirteen soluble antigens in common. However, fraction-specific antigens were also present. Thus, the extracts of the rough (R) membranes contained at least one typical antigen, not found in any of the other fractions. An antiserum against this component also precipitated a non-migrating antigen present only in the extracts of smooth (Sa) membranes. These two antigens may represent different molecular forms of a substance involved in binding of the ribosomes or in the assembly of membrane subunits. At least eleven of the antigens common for the two fractions exhibited enzymatic activities when assayed after precipitation with antibody in the immunoelectro- phoretic plates. Six immunologically and electrophoretically distinct antigens had esterase activity with α-naphthyl propionate as substrate. Two of these esterases also split indoxyl acetate. Three other antigens with acid phosphatase activity split both α-naphthyl acid phosphate and β-glycerophosphate. Three antigens had nucleoside diphosphatase activity when tested with uridine- or inosine-diphosphate. Preliminary experiments also suggested that two additional antigens possessed NADH-diaphorase activity and thus could belong to the microsomal electron trans- port systems. The third subfraction consisted of electron-microscopically smooth membranes (Sb), enzymatically different from those of the endoplasmic reticulum. The antigens typical for the latter were either absent or present only in minor and variable concentrations. Its extracts contained at least two typical antigens. One of these was identified as contaminating ferritin. The nature and origin of the other antigen has not yet been established. All antigens described in this paper were immunologically different from the common rat serum proteins. [ABSTRACT FROM AUTHOR]
- Published
- 1967
24. The paradoxical role of radiation‐induced cGAS–STING signalling network in tumour immunity.
- Author
-
Zhang, Xiaoyi, Zhang, Han, Zhang, Jiajia, Yang, Mengdie, Zhu, Mengqin, Yin, Yuzhen, Fan, Xin, and Yu, Fei
- Subjects
TUMOR microenvironment ,TYPE I interferons ,IMMUNITY ,RADIATION tolerance ,IMMUNE system - Abstract
The cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS–STING) pathway is an essential component of the innate immune system and is central to the identification of abnormal DNA leakage caused by ionising radiation (IR) damage. Cell‐intrinsic cGAS–STING initiation has been revealed to have tremendous potential for facilitating interferon synthesis and T‐cell priming. Targeting the cGAS–STING axis has been proposed as a strategy to improve radiosensitivity or enhance immunosurveillance. However, due to the complex biology of the irradiated tumour microenvironment and the extensive involvement of the cGAS–STING pathway in various physiological and pathological processes, many defects in this strategy limit the therapeutic effect. Here, we outline the molecular mechanisms by which IR activates the cGAS–STING pathway and analyse the dichotomous roles of the cGAS–STING pathway in modulating cancer immunity after radiotherapy (RT). Then, based on the crosstalk between the cGAS–STING pathway and other signalling events induced by IR, such as necroptosis, autophagy and other cellular effects, we discuss the immunomodulatory actions of the broad cGAS–STING signalling network in RT and their potential therapeutic applications. Finally, recent advances in combination therapeutic strategies targeting cGAS–STING in RT are explored. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
25. USP12 positively regulates M‐MDSC function to inhibit antitumour immunity through deubiquitinating and stabilizing p65.
- Author
-
Zhan, Xiaoxia, He, Qiuying, Sheng, Junli, Jiang, Xiaobing, Lin, Letao, Huang, Yulan, He, Shitong, Chen, Yitian, Li, Laisheng, Zeng, Zhijie, Hu, Shengfeng, Wang, Peng, and Zhang, Yanling
- Subjects
CYTOTOXIC T cells ,MYELOID-derived suppressor cells ,DEUBIQUITINATING enzymes ,NITRIC-oxide synthases ,IMMUNITY - Abstract
The relative abundance of myeloid‐derived suppressor cells (MDSCs) compared to cytotoxic T cells determines the outcomes of diseases and the efficacy of immunotherapy. Ubiquitin‐specific peptidase 12 (USP12), a member of the USP family of deubiquitinases, targets multiple signalling pathways and regulates diverse biological processes, including cell proliferation and survival. It is well known that ubiquitylation is an important mechanism for regulating the immune response. However, it is unclear whether USP12 regulates tumour growth by influencing MDSCs. In the present study, we reported that USP12 deficiency decreased infiltration and impaired the suppressor function of monocytic (M)‐MDSCs, resulting in increased CD8+ T‐cell response and decelerated tumour growth. USP12‐knockout M‐MDSCs were less potent in inhibiting the proliferation of CD8+ T cells and their ability to secrete IFN‐γ. Furthermore, USP12 deficiency inhibited the suppressor function of M‐MDSCs by downregulating the negative regulatory molecules inducible nitric oxide synthase and PD‐L1, through deubiquitinating and stabilizing p65. Our results suggest that USP12 is a positive regulator of M‐MDSCs and may serve as a potential target for antitumor therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
26. Heat inactivated mycobacteria, alpha‐Gal and zebrafish: Insights gained from experiences with two promising trained immunity inductors and a validated animal model.
- Author
-
Juste, Ramón A., Ferreras‐Colino, Elisa, de la Fuente, José, Domínguez, Mercedes, Risalde, María A., Domínguez, Lucas, Cabezas‐Cruz, Alejandro, and Gortázar, Christian
- Subjects
MYCOBACTERIA ,MYCOBACTERIUM bovis ,IMMUNITY ,BRACHYDANIO ,BACTERIAL cells ,PSYCHONEUROIMMUNOLOGY ,PLANT-pathogen relationships - Abstract
Trained immunity (TRAIM) may be defined as a form of memory where innate immune cells such as monocytes, macrophages, dendritic and natural killer (NK) cells undergo an epigenetic reprogramming that enhances their primary defensive capabilities. Cross‐pathogen protective TRAIM can be triggered in different hosts by exposure to live microbes or microbe‐derived products such as heat‐inactivated Mycobacterium bovis or with the glycan α‐Gal to elicit protective responses against several pathogens. We review the TRAIM paradigm using two models representing distinct scales of immune sensitization: the whole bacterial cell and one of its building blocks, the polysaccharides or glycans. Observations point out to macrophage lytic capabilities and cytokine regulation as two key components in non‐specific innate immune responses against infections. The study of the TRAIM response deserves attention to better characterize the evolution of host–pathogen cooperation both for identifying the aetiology of some diseases and for finding new therapeutic strategies. In this field, the zebrafish provides a convenient and complete biological system that could help to deepen in the knowledge of TRAIM‐mediated mechanisms in pathogen–host interactions. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
27. CIS and TGF‐β regulatory pathways influence immunity to bacterial infection.
- Author
-
McCulloch, Timothy R., Rossi, Gustavo R., Schreuder, Jaring, Belz, Gabrielle T., Wells, Timothy J., and Souza‐Fonseca‐Guimaraes, Fernando
- Subjects
BACTERIAL diseases ,INNATE lymphoid cells ,KILLER cells ,TRANSFORMING growth factors ,IMMUNITY - Abstract
Immunotherapy has revolutionized cancer therapy by reactivating tumour‐resident cytotoxic lymphocytes. More recently, immunotherapy has emerged to restore immunity against infectious agents, including bacterial infections. Immunotherapy primarily targets inhibitory pathways in T cells, however interest in other effector populations, such as natural killer (NK) cells, is growing. We have previously discovered that NK cell metabolism, proliferation and activation can be neutralized through the immunosuppressive transforming growth factor (TGF)‐β pathway by inducing plasticity of NK cells and differentiation into innate lymphoid cell (ILC)1‐like subsets. NK cells are also regulated through cytokine‐inducible SH2‐containing protein (CIS), which is induced by interleukin (IL)‐15 and is a potent intracellular checkpoint suppressing NK cell survival and function. Targeting these two distinct pathways to restore NK cell function has shown promise in cancer models, but their application in bacterial infection remains unknown. Here, we investigate whether enhancement of NK cell function can improve anti‐bacterial immunity, using Salmonella Typhimurium as a model. We identified conversion of NK cells to ILC1‐like for the first time in the context of bacterial infection, where TGF‐β signalling contributed to this plasticity. Future study should focus on identifying further drivers of ILC1 plasticity and its functional implication in bacterial infection model. We further describe that CIS‐deficient mice displayed enhanced pro‐inflammatory function and dramatically enhanced anti‐bacterial immunity. Inhibition of CIS may present as a viable therapeutic option to enhance immunity towards bacterial infection. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
28. Non‐structural protein 1‐specific antibodies directed against Zika virus in humans mediate antibody‐dependent cellular cytotoxicity.
- Author
-
Sanchez Vargas, Luis A., Adam, Awadalkareem, Masterson, Mary, Smith, Madison, Lyski, Zoe L., Dowd, Kimberly A., Pierson, Theodore C., Messer, William B., Currier, Jeffrey R., and Mathew, Anuja
- Subjects
ANTIBODY-dependent cell cytotoxicity ,KILLER cells ,ZIKA virus ,LYSIS ,IMMUNE serums - Abstract
There is growing interest in understanding antibody (Ab) function beyond neutralization. The non‐structural protein 1 (NS1) of Zika virus (ZIKV) is an attractive candidate for an effective vaccine as Abs against NS1, unlike the envelope or premembrane, do not carry the risk of mediating antibody‐dependent enhancement. Our aim was to evaluate whether ZIKV NS1 Abs elicited following natural infection in humans can mediate antibody‐dependent cellular cytotoxicity (ADCC). We evaluated the isotype specificity of ZIKV‐specific Abs in immune sera and supernatants from stimulated immune PBMC and found that Abs against ZIKV NS1 and virus‐like particles were predominantly of the IgG1 isotype. Using a recently developed FluoroSpot assay, we found robust frequencies of NS1‐specific Ab‐secreting cells in PBMC of individuals who were naturally infected with ZIKV. We developed assays to measure both natural killer cell activation by flow cytometry and target cell lysis of ZIKV NS1‐expressing cells using an image cytometry assay in the presence of ZIKV NS1 Abs. Our data indicate efficient opsonization of ZIKV NS1‐expressing CEM‐NKR cell lines using ZIKV‐immune but not ZIKV‐naïve sera, a prerequisite of ADCC. Furthermore, sera from immune donors were able to induce both NK cell degranulation and lysis of ZIKV NS1 CEM‐NKR cells in vitro. Our data suggest that ADCC is a possible mechanism for ZIKV NS1 Abs to eliminate virally infected target cells. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
29. Immunity and repair in the nervous system<BR/>(BSI Neuroimmunology Affinity Group).
- Subjects
- *
IMMUNOLOGY , *IMMUNITY , *NERVOUS system - Abstract
Presents abstracts of research papers on immunity and repair in the nervous system, published in the December 2002 supplement of 'Immunology.' 'The Immunobiology of TSE diseases,' by N.A. Mabbott; 'Autoimmunity in the peripheral nervous system: An overview,' by H.J. Willison.
- Published
- 2002
- Full Text
- View/download PDF
30. The turning away of serum amyloid A biological activities and receptor usage.
- Author
-
Abouelasrar Salama, Sara, Gouwy, Mieke, Van Damme, Jo, and Struyf, Sofie
- Subjects
EXTRACELLULAR matrix proteins ,AMYLOID ,LIPOPROTEINS ,LIPOPOLYSACCHARIDES ,TOLL-like receptors - Abstract
Summary: Serum amyloid A (SAA) is an acute‐phase protein (APP) to which multiple immunological functions have been attributed. Regardless, the true biological role of SAA remains poorly understood. SAA is remarkably conserved in mammalian evolution, thereby suggesting an important biological function. Since its discovery in the 1970s, the majority of researchers have investigated SAA using recombinant forms made available through bacterial expression. Nevertheless, recent studies indicate that these recombinant forms of SAA are unreliable. Indeed, commercial SAA variants have been shown to be contaminated with bacterial products including lipopolysaccharides and lipoproteins. As such, biological activities and receptor usage (TLR2, TLR4) revealed through the use of commercial SAA variants may not reflect the inherent nature of this APP. Within this review, we discuss the biological effects of SAA that have been demonstrated through more solid experimental approaches. SAA takes part in the innate immune response via the recruitment of leucocytes and executes, through pathogen recognition, antimicrobial activity. Knockout animal models implicate SAA in a range of functions, such as regulation of T‐cell‐mediated responses and monopoiesis. Moreover, through its structural motifs, not only does SAA function as an extracellular matrix protein, but it also binds extracellular matrix proteins. Finally, we here also provide an overview of definite SAA receptor‐mediated functions and highlight those that are yet to be validated. The role of FPR2 in SAA‐mediated leucocyte recruitment has been confirmed; nevertheless, SAA has been linked to a range of other receptors including CD36, SR‐BI/II, RAGE and P2RX7. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
31. Sex difference in delayed footpad reaction to syngeneic testicular cells in C3H/He mice.
- Subjects
SEX differences (Biology) ,ANTIGENS ,IMMUNIZATION ,IMMUNITY ,IMMUNOLOGY ,LYMPHOCYTES - Abstract
Delayed footpad reaction against syngeneic testicular cells was compared between males and virgin females of C3H/He mice. Mice were immunized subcutaneously with 1 × 10
7 of syngeneic testicular cells and the reaction was elicited with 1 × 106 of syngeneic testicular cells 6 days after the immunization. When mice were pretreated with 0, 25 or 50 mg/kg of cyclophosphamide (CY), the delayed footpad reaction was detected in female mice, but not in male mice under the same conditions. This sex difference in the reaction to testicular cells was not attributed to the recognition of H-Y antigen by female mice. A sex difference in the reaction to sheep red blood cells (SRBC) was not observed. The sex difference in the reaction to testicular cells was attributed to testicular cells other than sperm because a sex difference was not detected against sperm. The implications of these findings are discussed in relation to the tolerance phenomena of autologous testicular cells. [ABSTRACT FROM AUTHOR]- Published
- 1983
32. Interference of propamidine with binding of the fifth component of complement to surface-fixed C3b, and with C5 activation.
- Author
-
Vogt, W., Schmidt, Gisa, and Hinsch, Bärbel
- Subjects
ANTI-infective agents ,COMPLEMENT (Immunology) ,BLOOD proteins ,HEMOLYSIS & hemolysins ,IMMUNITY ,ANTIGEN-antibody reactions - Abstract
The effects of propamidine and their dose dependency, on utilization of the third and fifth complement components in immune haemolysis have been compared. While C3 utilization is not disturbed that of CS is markedly inhibited by propamidine in concentrations as low as 0.5 mist Both, binding of CS to surface-fixed C3b and cleavage of CS by convertases C42 and C3bBb, are also inhibited in the presence of propamidine. Since neither C3 cleavage by these enzymes nor even C5 cleavage by the cobra venom factor-supported convertase CFVBb is significantly reduced a general convertase-inhibiting effect of propamidine is ruled out. Rather the effect on utilization of C5 is the result of interference with binding of CS to C3b and hence impairment of its accessibility to the convertases. These findings thus further support the role of surface-fixed C3b in C5 activation proposed earlier. [ABSTRACT FROM AUTHOR]
- Published
- 1979
33. The purification of specific anti-picryl T suppressor factor which depresses the passive transfer of contact sensitivity: affinity chromatography on antigen and Concanavalin A sepharose and specific elution with hapten and α-methylmannoside.
- Author
-
Asherson, G. L., Zembala, M., and Noworolski, J.
- Subjects
LYMPHOID tissue ,IMMUNE system ,AGAR ,AMINO acids ,IMMUNE complexes ,IMMUNE response ,IMMUNITY ,IMMUNOLOGY ,ALBUMINS - Abstract
Anti-picrylsuppressor factor was prepared in the standard way, i.e. by culturing lymphoid cells from mice injected with picrysulphonic acid and then painted with picryl chloride and taking the supernatant fluid. It was assessed by its ability to depress the passive transfer of contact sensitivity by immune cells incubated in it. The factor can be specifically absorbed by picryl (but not oxazolone) albumin sepharose beads and can be specifically eluted by picryl (but not oxazolone) ϵ-aminocaproic acid and by picryl-ϵ-N-lysine. These findings emphasise the role of the hapten epitope in the binding of a specific T cell product. The factor can also be absorbed by Concanavalin A sepharose and can be eluted by an appropriate sugar such as ɑ-methylmannoside, but not by an inappropriate sugar such as lactose. It was possible to undertake two sequential affinity chromatography steps—first absorption with picryl albumin sepharose and elution with picryl-ϵ-N-lysine followed immediately by absorption by Con A sepharose and elution with α-methylmannoside. The availability of sequential affinity chromatography provides a simple approach to the purification of specific T suppressor factor. [ABSTRACT FROM AUTHOR]
- Published
- 1978
34. Serum Factors Affecting the Incorporation of [3]Thymidine by Lymphocytes Stimulated by Antigen. I. SERUM CONCENTRATION.
- Author
-
Forsdyke, D. R.
- Subjects
SERUM ,THYMIDINE ,LYMPHOCYTES ,ANTIGENS ,LYMPH nodes ,CELLS ,LABORATORY rats ,IMMUNITY - Abstract
Lymph node cells from immunized rabbits were cultured with varying concentrations of antigen in preheated (56°, 30 minutes) autologous serum which had been collected before immunization. [
3 H]Thymidine was present for the last 6 hours of the 24-hour culture period and the radioactive labelling of acid-precipitable material was then determined. Changes in labelling due to variations of culture conditions were interpreted according to whether they were specific for control or antigen-treated cultures or non-specific. Cell concentration and serum concentration were predominantly non-specific variables influencing the labelling in control and antigen-treated cultures to a proportionate extent. However, at serum concentrations below 5 per cent labelling was disproportionately inhibited in antigen-treated cultures; there were further minor disproportionate inhibitions at higher serum concentrations. Labelling was inhibited by increasing the concentration of serum from 25 to 50 per cent, mainly due to a non-diffusible competitive inhibitory activity. Isotope-dilution analysis of the effects of serum on labelling over a wide range of serum concentrations indicated that the relationship was a complex one with at least three step-wise stimulations of the maximum labelling rate being produced by increasing the serum concentrations from 0 to 25 per cent. Labelling in antigentreated cultures containing post-immunization serum was less than labelling in cultures containing an equal volume of preimmunization serum, but labelling in control cultures was enhanced by post-immunization serum. These results are shown to be compatible with the proposals (i) that labelling in control cultures reflects the response of cells to low concentrations of endogenous antigens, and (ii) that preimmunization serum and post-immunization serum contain ‘natural’ and ‘acquired’ antibodies respectively, which normally buffer cell-borne receptor sites against reaction with endogenous and exogenous antigens. [ABSTRACT FROM AUTHOR]- Published
- 1973
35. Immunological Unresponsiveness to Protein Antigens in Rabbits. I. THE DURATION OF UNRESPONSIVENESS FOLLOWING A SINGLE INJECTION AT BIRTH.
- Author
-
Humphrey, J.H.
- Subjects
IMMUNOGLOBULINS ,IMMUNITY ,LABORATORY rabbits ,ANTIGENS ,IMMUNE response ,IMMUNOLOGY - Abstract
The immunological responses of rabbits to HSA, HGG or BSA were tested at various times later in animals which had received the corresponding antigens before or shortly after birth. As judged by the criterion of failure to show immune elimination of antigen, a high proportion of the rabbits remained unresponsive at times when it was calculated that all the originally administered antigen would have been eliminated from the circulation. Furthermore, removal of antigen by passively administered antibody failed to restore the capacity to respond. It is concluded that, in respect of the antigens used, their persistence in the extracellular body fluids is not a prerequisite for maintenance of immunological unresponsiveness.
Further administration of the same antigen to rabbits which had escaped from a state of specific immunological unresponsiveness generally produced a very weak response, and in a few instances resulted in a return to the unresponsive state.
When the cross-reacting antigens HSA and BSA were administered adsorbed on alum to rabbits made unresponsive by neonatal contact with BSA and HSA respectively, and at the same time a further dose of the original antigen was given, antibodies were formed which were specific for the second antigen and did not cross-react with the first. In only 1/9 animals was responsiveness to the first antigen restored. The significance of these results is discussed. [ABSTRACT FROM AUTHOR]- Published
- 1964
36. The Significance of the Protein Carrier in the Stimulation of DNA Synthesis by Hapten-Protein Conjugates in the Secondary Response.
- Author
-
Dutton, R. W. and Bulman, Harriet N.
- Subjects
DNA synthesis ,IMMUNITY ,LABORATORY animals ,DINITROBENZENES ,ANTIGENS ,PROTEINS - Abstract
Rabbits were immunized with 2,4-dinitrophenyl (DNP)-protein conjugates. Spleen cell suspensions were prepared and incubated in the presence of various DNP protein conjugates, the proteins alone, and DNP-lysine. The antigen dependent stimulation of DNA synthesis was used as a measure of the antigenic ‘activity’ of the DNP preparations. It was found that the cells were strongly stimulated by the DNP-protein conjugates used for immunization, and weakly stimulated by the protein alone. Highly substituted DNP protein conjugates were markedly more effective than lightly substituted conjugates. DNP-conjugates with proteins other than the one used during immunization were inactive. DNP-lysine alone was inactive but inhibited stimulation by the DNP protein conjugate used for immunization. The significance of these findings is discussed. [ABSTRACT FROM AUTHOR]
- Published
- 1964
37. Tolerance of Erythrocytes in Poultry: Loss and Abolition.
- Author
-
Mitchison, N.A.
- Subjects
ERYTHROCYTES ,IMMUNOLOGICAL tolerance ,POULTRY physiology ,IMMUNOLOGY ,CELLULAR immunity ,IMMUNITY - Abstract
Fowls which tolerate foreign erythrocytes, but which have not received a transplant of variable cells, eventually lose tolerance when the supply of erythrocytes is discontinued. The loss follows, at an interval, after the foreign erythrocytes have been eliminated by the normal mechanism for removal of aged cells; earlier loss can be brought about by eliminating the foreign cells with passive antibody. The interval required for loss varies, for tolerance of homologous erythrocytes, from less than 5 to over 215 days. The age of the tolerance bird, and hence the duration of exposure to antigen, is the main factor influencing the interval required; the preceding level of tolerance exerts comparatively little effect. An attempt to terminate tolerance by adoptive immunization was only partially successful. [ABSTRACT FROM AUTHOR]
- Published
- 1962
38. Interaction of a Serum Inhibitor of C'I-Esterase with Intermediate Complexes of the Immune Haemolytic System II. KINETICS AND MECHANISM OF THE INTERACTION.
- Author
-
Leon, M.A. and Lepow, I.H.
- Subjects
ESTERASES ,HYDROLASES ,ERYTHROCYTES ,HEMOLYSIS & hemolysins ,IMMUNITY ,SHEEP - Abstract
The kinetics of the reaction between C' I-esterase inhibitor and an intermediate complex of sensitized sheep erythrocytes and human complement are described. The rate of reaction was directly proportional to the concentrations of both inhibitor and intermediate complex, but was insensitive to changes in pH over the range 7.4 - 8.7 and in ionic strength from 0.15 - 0.24. The rate of reaction was accelerated b an increase in temperature over the range 22° - 37°. The experimental evidence was consistent with a mechanism picturing the reaction of C' I-esterase inhibitor with C' I-esterase bound to the intermediate complex. A theoretical treatment is described from which values for various kinetic and thermodynamic quantities may be calculated. [ABSTRACT FROM AUTHOR]
- Published
- 1962
39. Immunoglobulin Determinants on the Lymphocytes of Normal Rabbits II. DIFFICULTY IN DEMONSTRATING THE <em>a</em> LOCUS DETERMINANTS As1, 2 AND 3 BY THE MIXED ANTIGLOBULIN REACTION.
- Author
-
Wolf, B., Coombs, R. R. A., Gell, P. G. H., and Kelus, A. S.
- Subjects
IMMUNOGLOBULINS ,LYMPHOCYTES ,LEUCOCYTES ,RABBITS ,IMMUNITY ,IMMUNOLOGY - Abstract
Summary. Rabbit circulating lymphocytes have been examined for the a locus allotypic markers As1, As2 and As3 using the mixed antiglobulin reaction. These determinants cannot be as easily demonstrated as the b locus determinants As4, As5 and As6. Undiluted antiserum is required and even then the percentage of reacting cells is low. The specificity of the reaction was checked by an inhibition procedure. [ABSTRACT FROM AUTHOR]
- Published
- 1970
40. Antigenic Stimulation of Bone Marrow Colony Forming Cells II. PROPERTIES OF A SERUM FACTOR RESPONSIBLE FOR ANTIGENIC ENHANCEMENT OF COLONIES.
- Author
-
McNeill, T.A.
- Subjects
ANTIGENS ,IMMUNITY ,IMMUNOGLOBULINS ,IMMUNE response ,BONE marrow ,BONE marrow cells - Abstract
The enhancement effect of some antigens on in vitro colony formation by normal mouse bone marrow cells is mediated through a normal serum αmacroglobulin (αM) which is present in newborn animals and shows no immunological specificity. The proportion of antigen and αM affects colony enhancement, and it has also been shown that specific antibody successfully competes with αM for the antigen. It seems likely that antigen-αM complex acts directly on the colony forming cell, rather than indirectly through release of colony stimulating factor. The possible relevance of this phenomenon to immune induction and, to the effect of antigens in promoting irradiation survival is discussed. [ABSTRACT FROM AUTHOR]
- Published
- 1970
41. Analysis of Soluble Antigens in Guinea-Pig Epidermis.
- Author
-
Aoki, T., Parker, Darien, and Turk, J.L.
- Subjects
ANTIGENS ,IMMUNITY ,IMMUNOGLOBULINS ,GUINEA pigs ,CAVIIDAE ,IMMUNOLOGY - Abstract
Five tissue specific antigens in guinea-pig epidermis were characterized by heat treatment, enzyme digestion, DEAE-cellulose chromatography, (NH
4 )2 SO4 precipitation, ethanol precipitation and gel filtration. These antigens appeared to be proteins although one was fairly resistant to proteinases. Two antigens (Sp2a and Sp2b) were heat-stable and precipitated at high (NH4 )2 SO4 concentration (3.0 M—saturation): Sp2b was also precipitated at very high ethanol concentration (50-90 per cent). On electrophoresis, Sp2a was shown to have three distinct molecules, while Sp2b showed two. The molecular weight of one component of Sp2a was 71,000 and that of one component of Sp2b was 13,500, as determined by gel filtration. A third antigen behaved electrophoretically and chromatographically like γ-globulin, but was separated from it by (NH4 )2 SO4 precipitation. The other two antigens did not show any characteristic features and behaved like many other non-specific tissue antigens. [ABSTRACT FROM AUTHOR]- Published
- 1969
42. The Short-Term Culture of Lymphoid Tissue from Immunized Guinea-Pigs.
- Author
-
Dresser, Ann M.
- Subjects
LYMPHOID tissue ,GUINEA pigs as laboratory animals ,IMMUNOGLOBULINS ,IMMUNOLOGY ,IMMUNITY ,IMMUNE system - Abstract
Lymph node tissue from guinea-pigs immunized against one of several antigens was cultured in different media in order to determine conditions under which maximal amounts of antibody are formed in vitro. The amounts of antibody formed were variable and bore no relation m the level of serum antibody in the tissue donor. Heterologous sera of several origins, when included in the culture medium, varied very markedly in their capacity to support antibody production in vitro. [ABSTRACT FROM AUTHOR]
- Published
- 1965
43. 'Just 17 if you know what I mean' ... but what do we really mean to say about Th17 immunity?
- Author
-
Altmann, Daniel M.
- Subjects
IMMUNITY - Abstract
Summary : Th17‐derived IL‐17 might be considered the archetypal pro‐inflammatory cytokine of adaptive immunity, to be targeted by new therapeutics for alleviation of autoimmune and inflammatory disease. However, the IL‐17 family of cytokines is produced by diverse innate and adaptive cells, including Th17, Tc17, ILC3, NK cells and γδ T‐cells. These responses are appreciated to underpin diverse aspects of protective, physiological immunity, from dialogue with the gut microbiota to bacterial and fungal immunity in the lung. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
44. Neuromedin U: potential roles in immunity and inflammation.
- Author
-
Ye, Yuan, Liang, Zongan, and Xue, Luzheng
- Subjects
SMOOTH muscle contraction ,INFLAMMATION ,IMMUNITY ,SPINAL cord - Abstract
Summary: Since the discovery of neuromedin U (NmU) from porcine spinal cord in 1985, this neuropeptide has been subsequently identified in many other species with multiple physiological and pathophysiological roles detected, ranging from smooth muscle contraction, feeding, energy balance to tumorigenesis. Intriguingly, NmU is also emerging to play pro‐inflammatory roles involving immune cell activation and cytokine release in a neuron‐dependent or neuron‐independent manner. The NmU‐mediated inflammatory responses have already been observed in worm infection, sepsis, autoimmune arthritis and allergic animal models. In this review, we focus on the roles of NmU in immunity and inflammation by highlighting the interactions between NmU and immune cells, summarizing the signalling mechanism involved in their reactions and discussing its potential contributions to inflammatory diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
45. Circadian rhythms in adaptive immunity.
- Author
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Downton, Polly, Early, James O., and Gibbs, Julie E.
- Subjects
CIRCADIAN rhythms ,IMMUNE response ,IMMUNITY ,MOLECULAR clock ,PARASITIC diseases - Abstract
Summary: The circadian clock provides organisms with the ability to track time of day, allowing them to predict and respond to cyclical changes in the external environment. In mammals this clock consists of multiple auto‐regulatory feedback loops generated by a network of circadian clock proteins. This network provides the fundamental basis for rhythms in behaviour and physiology. This clockwork machinery exists in most cells, including those of the immune system. In recent years evidence has emerged highlighting the important role of molecular clocks in dictating the response of immune pathways. While initial work highlighted the effect of the clock in the 'first line of defence', the innate immune system, it has become increasingly apparent that it also plays a role in the more tailored, later‐stage adaptive immune response. This review provides an overview of the role of the circadian cycle in the adaptive immune response. We interrogate the depth of knowledge on cell intrinsic clocks within adaptive immune cells and how these cells may be temporally directed by extrinsic rhythmic signals. We discuss the role of the circadian clock in diseases associated with adaptive immunity such as multiple sclerosis, asthma and parasitic infection. We also discuss the current knowledge on timing of vaccination, and the implications this may have on how we can harness and modulate temporal gating of the adaptive immune response in a clinical setting. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
46. Skin barrier immunity and ageing.
- Author
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Chambers, Emma S. and Vukmanovic‐Stejic, Milica
- Subjects
MACROPHAGES ,SUPPRESSOR cells ,LANGERHANS cells ,BODY surface area ,IMMUNITY ,PSYCHONEUROIMMUNOLOGY - Abstract
Summary: The skin is the outermost layer of the body with an extensive surface area of approximately 1·8 m2, and is the first line of defence against a multitude of external pathogens and environmental insults. The skin also has important homeostatic functions such as reducing water loss and contributing to thermoregulation of the body. The structure of the skin and its cellular composition work in harmony to prevent infections and to deal with physical and chemical challenges from the outside world. In this review, we discuss how the structural cells such as keratinocytes, fibroblasts and adipocytes contribute to barrier immunity. We also discuss specialized immune cells that are resident in steady‐state skin including mononuclear phagocytes, such as Langerhans cells, dermal macrophages and dermal dendritic cells in addition to the resident memory T cells. Ageing results in an increased incidence of cancer and skin infections. As we age, the skin structure changes with thinning of the epidermis and dermis, increased water loss, and fragmentation of collagen and elastin. In addition, the skin immune composition is altered with reduced Langerhans cells, decreased antigen‐specific immunity and increased regulatory populations such as Foxp3+ regulatory T cells. Together, these alterations result in decreased barrier immunity in the elderly, explaining in part their increased susceptiblity to cancer and infections. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
47. Human dendritic cell subsets: an update.
- Author
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Collin, Matthew and Bigley, Venetia
- Subjects
DENDRITIC cells ,HEMATOPOIESIS ,IMMUNITY ,TRANSCRIPTION factors ,MONOCYTES - Abstract
Summary: Dendritic cells (DC) are a class of bone‐marrow‐derived cells arising from lympho‐myeloid haematopoiesis that form an essential interface between the innate sensing of pathogens and the activation of adaptive immunity. This task requires a wide range of mechanisms and responses, which are divided between three major DC subsets: plasmacytoid DC (pDC), myeloid/conventional DC1 (cDC1) and myeloid/conventional DC2 (cDC2). Each DC subset develops under the control of a specific repertoire of transcription factors involving differential levels of IRF8 and IRF4 in collaboration with PU.1, ID2, E2‐2, ZEB2, KLF4, IKZF1 and BATF3. DC haematopoiesis is conserved between mammalian species and is distinct from monocyte development. Although monocytes can differentiate into DC, especially during inflammation, most quiescent tissues contain significant resident populations of DC lineage cells. An extended range of surface markers facilitates the identification of specific DC subsets although it remains difficult to dissociate cDC2 from monocyte‐derived DC in some settings. Recent studies based on an increasing level of resolution of phenotype and gene expression have identified pre‐DC in human blood and heterogeneity among cDC2. These advances facilitate the integration of mouse and human immunology, support efforts to unravel human DC function
in vivo and continue to present new translational opportunities to medicine. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
48. Evaluating antidisease immunity to malaria and implications for vaccine design.
- Author
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Ademolue, Temitope W. and Awandare, Gordon A.
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MALARIA ,DRUG design ,IMMUNITY ,INFLAMMATION ,EVIDENCE-based medicine ,VACCINATION - Abstract
Summary: Immunity to malaria could be categorized broadly as antiparasite or antidisease immunity. While most vaccine research efforts have focused on antiparasite immunity, the evidence from endemic populations suggest that antidisease immunity is an important component of natural immunity to malaria. The processes that mediate antidisease immunity have, however, attracted little to no attention, and most interests have been directed towards the antibody responses. This review evaluates the evidence for antidisease immunity in endemic areas and discusses the possible mechanisms responsible for it. Given the key role that inflammation plays in the pathogenesis of malaria, regulation of the inflammatory response appears to be a major mechanism for antidisease immunity in naturally exposed individuals. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
49. The composition of immune cells serves as a predictor of adaptive immunity in a cohort of 50- to 74-year-old adults.
- Author
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Kennedy, Richard B., Simon, Whitney L., Gibson, Michael J., Goergen, Krista M., Grill, Diane E., Oberg, Ann L., and Poland, Gregory A.
- Subjects
IMMUNITY ,INFLUENZA ,INFLUENZA vaccines ,IMMUNOSENESCENCE ,FLOW cytometry ,PATIENTS - Abstract
Influenza causes significant morbidity and mortality annually. Although vaccination offers a considerable amount of protection, it is far from perfect, especially in aging populations. This is due to age-related defects in immune function, a process called immunosenescence. To date, there are no assays or methods to predict or explain variations in an individual's level of response to influenza vaccination. In this study, we measured levels of several immune cell subsets at baseline (Day 0) and at Days 3 and 28 post-vaccination using flow cytometry. Statistical modelling was performed to assess correlations between levels of cell subsets and Day 28 immune responses - haemagglutination inhibition ( HAI) assay, virus neutralizing antibody ( VNA) assay, and memory B cell ELISPOT. Changes in several groups of cell types from Day 0 to Day 28 and Day 3 to Day 28 were found to be significantly associated with immune response. Baseline levels of several immune cell subsets, including B cells and regulatory T cells, were able to partially explain variation in memory B-cell ELISPOT results. Increased expression of HLA- DR on plasmacytoid dendritic cells after vaccination was correlated with increased HAI and VNA responses. Our data suggest that the expression of activation markers ( HLA- DR and CD86) on various immune cell subsets, as well as the relative distribution of cell subsets, both have value in predicting immune responses to influenza vaccination in older individuals. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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50. Subject Index.
- Subjects
- *
IMMUNOLOGY , *SEROLOGY , *IMMUNITY , *IMMUNE system , *PROTEINS , *VIRAL proteins - Abstract
Presents an index of the subjects of research papers published in the 1988 issues of the periodical "Immunology,". C-reactive protein; CD4+ cells; HIV proteins; Eosinophils.
- Published
- 1989
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